Surprisingly moving for a film assembled from such familiar scenes, Craig Johnson's The Skeleton Twins mushes together queasy/quirky indie family drama with the beats of a romantic comedy. You know the outline just from eyeballing the poster: Kristen Wiig's Maggie and Bill Hader's Milo find their way toward loving each other after a wary start. Then, not long after they've found each other, and after Johnson has stopped positioning them on the far opposite sides of the frame, and after we've had the chance to relish their giddy togetherness, backstory must rip them apart.

What's singular here isn't that the stars are playing brother and sister, or that they stir such sublime and anxious joy from each other. It's that the real love story isn't even between the damaged-but-lovable characters. It's between two profoundly depressed people and life itself. The movie's honest about what a struggle the day to day can be for too many people — it gets that, like a prospective romantic partner, a reason for living can play awfully hard to get.

That's not to say The Skeleton Twins is a grind. Most movies that kick off with multiple attempted suicides aren't this funny. And movies in which comedy stars dial back and play serious are never this funny. Most of the laughs come from well-observed human behavior: In the opening scenes, Wiig's Maggie visits Milo in the hospital after he's tried to kill himself. For reasons the script is too coy about revealing, the siblings have not seen each other in a decade, and at first Milo can only speak to her the way they did as teenagers: via shtick and complaints. A hostile exchange about Marley & Me is hilarious in the way that people are and movies usually aren't: One character, not sure how to handle the other, lashes out, joking to slow the exposure of messier feelings.

Milo moves into Maggie's house in their hometown in upstate New York, studying the cracks in her marriage to a nice guy (Luke Wilson) neither respects. The best scenes come as the siblings discover how to be around each other — and get close to discovering how to be, period. Getting there, The Skeleton Twins finds new life in the most shopworn of scenarios: An uptight character gets high and loosens up, in this case on nitrous oxide that sends Wiig (the one who needed loosening) and Hader into confessions and fits of fart-dancing on the floor of a dentist's office. The scene is long and nourishing; it stirs that feeling of raw, unguarded safety you might share with the people who have known you best and longest. Even the obligatory out-of-nowhere musical number has the power to seize viewers' guts: To haul Maggie out of the foulest of moods, Milo lip-syncs to the only god-awful '80s synth-pop hit that hasn't yet been mined for a nostalgic movie moment. (But it was in Mannequin.) Director Johnson and his cast hit a chord of feeling more complex than those on the soundtrack. Milo's funny as he fake-sings but also annoying, and when the chorus hits, Maggie — furious, unwilling to crack — refuses to join him. Johnson lets the full song play out, and we witness the characters negotiate their moods, their pride, their present, and their past in what feels like real time. It's a wonderful one-act play, as is the fight the two have late in the film over their unresolved past. Just as no one can make these two happier than each other, nobody else can hurt each other more.

Not everything is so shrewdly judged. Hader's Milo is gay, and the character is dramatic and performative, but I still doubt he would bust into Maggie's bedroom — where she's sleeping with the husband who just met Milo a day or so before — and carp drunkenly about his failure to find "cock" in his hometown bar. (Also dispiriting: Milo, given a job clearing brush at a dam, chirps, "Do I get a sexy outfit?")

Wilson plays the husband, a sturdy and smiling fellow the movie condescends to — he's into hunting and Pizza Pockets, and every line he speaks sounds like the writer-director finds nothing more noxious than niceness. The film's low point is a visit from the siblings' New Age mother (Joanna Gleason), which plays like bitter sketch comedy and suffers from confounding logistics. And one impassioned speech from Hader unintentionally lays bare the self-regard of the people who get paid too much to make movies: Here's a famous actor playing a regular person whining at length that he never got to be a famous actor.

Fifteen ill-conceived minutes aside, The Skeleton Twins confirms the good sense of Kristen Wiig. Rather than go bigger and bigger in sequels and studio comedies, she goes deeper into character. Her Maggie holds her face blank, not trusting the world to know anything of her except her rages. Tenderly, exhibiting a rare understanding of prickly nervousness, Wiig reveals the uncertain soul trembling beneath the impassive mask. Skeleton Twins isn't perfect, but it cuts to the bone.